The continuing evolution in medical care, adoption of high technology therapies, and advances in blood banking technology have led to innovations in transfusion therapy. Wise decisions about the use of novel blood products and the management of hemostatic disorders has created a need for a national clinical trials network to evaluate new therapies. The University of Minnesota has a long history of successful transfusion medicine and hemostasis clinical trials. There is an excellent productive relationship between key clinical services and hemostasis and transfusion medicine. The resources to successfully produce novel blood products or to provide new therapies for hemostatic conditions are available through our Molecular and Cellular Facility and Cell Therapy Laboratory and through excellent relationships with traditional blood suppliers. Therefore we propose a transfusion medicine and a hemostasis protocol each of which addresses important clinical issues that need scientific study in a muiticenter network. Preliminary studies have suggested that doses of platelets substantially higher or lower than present practice might lead to an overall reduction in the need for platelets while maintaining adequate hemostasis in thrombocytopenic patients. Therefore, our first proposed trial will compare doses of platelets two times larger and half as large with the present standard dose of platelets for their ability to maintain hemostasis in thrombocytopenic patients. The second clinical trial will compare plasma exchange with high dose steroids for the treatment of thrombotic microangiopathy (TM) secondary to solid organ or stem cell transplantation. Plasma exchange is clearly beneficial in patients with thrombotic thrombocytopenic purpura but TM secondary to transplantation has a different pathophysiologic mechanism and the optimum treatment for this form of TM is not known. This trial will add to the understanding of the management of this difficult clinical situation and will determine which of these therapies is most efficacious. We believe these clinical trials address two extremely important issues; their design illustrates our ability to develop clinical trials and the supportive resource description establishes our ability to provide novel blood components and carry out successful clinical trials. The investigators in this project and other leaders of major clinical programs at the University of Minnesota are interested and willing to participate in these and other clinical trials that may be developed through this network.